Blastocyst-stage mouse embryos will be cultured with fragments of isolated uterine epithelium under conditions where they attach and begin to invade. With this culture system the histological architecture of the epithelium is maintained and no artificial substrata are present to complicate the interpretation. To control changes simply due to the culture system, all studies will require six types of culture: isolated epithelium and blastocysts will be cultured separately and together, and each of these types of cultures will be studied before and after the time when adhesion is first seen. (1) Observations of the surface topography will be made with the transmission and scanning electron microscopes. In addition, comparisons will be made between attachment to uterine epithelium and other types of epithelium. (2) The biosynthesis of radioisotopically-labeled surface glycoproteins and proteoglycans will be examined initially through one- and two-dimensional gel electrophoresis of homogenates of entire cultures and then through detailed analyses of these macromolecules isolated from the cell surface. The analyses will involve the techniques of gel exclusion, ion exchange, and thin layer chromatography; density gradient centrifugation; specific enzyme susceptibility; and cellulose acetate strip and SDS-polyacrylamide gel electrophoresis. Analyses will be made first of the specific isolated glycosaminoglycans and oligosaccharides and second of the intact protein-containing polymer. (3) The role of cell surface sugars in blastocyst adhesion will be studied by attempting to modify them with enzymes which cleave specific sugars and by inhibitors of polysaccharide synthesis.